A randomized, placebo-controlled comparison of oral valacyclovir and acyclovir in immunocompetent patients with recurrent genital herpes infections. The Valaciclovir International Study Group.

OBJECTIVE To compare valacyclovir hydrochloride with acyclovir in the treatment of recurrent genital herpes infection. DESIGN A multicenter, double-blind, placebo-controlled, randomized, parallel-design study. SETTING University clinics (dermatology, gynecology, and infectious diseases) and private practices. PATIENTS One thousand two hundred patients with recurrent genital herpes simplex infections. INTERVENTIONS Patients self-initiated oral therapy with 1000 mg of valacyclovir hydrochloride twice daily, 200 mg of acyclovir 5 times daily, or placebo for 5 days. MAIN OUTCOME MEASURES Resolution of all signs and symptoms of recurrent genital herpes infection. RESULTS Both drugs were significantly more effective than placebo in speeding resolution of herpetic episodes (median duration, 4.8, 4.8, and 5.9 days, respectively); the hazards ratios for valacyclovir and acyclovir vs placebo were 1.66 (95% confidence interval [CI], 1.38-2.01) and 1.71 (95% CI, 1.41-2.06) (both P < .001). Similarly, valacyclovir and acyclovir significantly hastened lesion healing (hazards ratios vs placebo were 1.88 [95% CI, 1.53-2.32] and 1.90 [95% CI, 1.55-2.34], respectively; P < .001). Pain duration was shorter in valacyclovir- and acyclovir-treated patients (median, 2 vs 3 days). Viral shedding stopped 2.55 times faster in patients treated with valacyclovir and 2.24 times faster in patients treated with acyclovir than in patients treated with placebo. Aborted episodes, in which lesions did not progress beyond the macule or papule stage, tended to occur in more patients treated with valacyclovir (25.9%) or acyclovir (24.8%) than in patients treated with placebo (19.8%). Valacyclovir and acyclovir did not differ significantly with regard to their respective effects on any of the above efficacy parameters. The nature, severity, and frequency of adverse events did not differ among the 3 treatment groups. CONCLUSIONS Twice-daily valacyclovir was as effective and well tolerated in the treatment of recurrent genital herpes simplex virus infection as 5-times-daily acyclovir. Therefore, valacyclovir could prove a useful alternative to acyclovir when convenience of dosing or compliance issues are the prime considerations in treatment.